Journal of Biopharmaceutical Statistics最新文献_第6页

An investigation to improve a nonlinear mixed-effects approach for EC50 estimation based on multi-donor dose-response data. 基于多供体剂量反应数据的 EC50 估算非线性混合效应方法的改进研究。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-11-06 DOI: 10.1080/10543406.2024.2421424

Weiliang Qiu, Cheng Wenren, Els Pattyn, Tamara Slavnic, Luc Esserméant

{"title":"An investigation to improve a nonlinear mixed-effects approach for EC50 estimation based on multi-donor dose-response data.","authors":"Weiliang Qiu, Cheng Wenren, Els Pattyn, Tamara Slavnic, Luc Esserméant","doi":"10.1080/10543406.2024.2421424","DOIUrl":"https://doi.org/10.1080/10543406.2024.2421424","url":null,"abstract":"Dose-response relationships are important in assessing the efficacy and potency of compounds, which can usually be characterized by a 4-parameter logistic (4-PL) model estimating EC50, slope factor, lower asymptote, and upper asymptote. EC50, the concentration of a compound that induces a response halfway between the baseline and maximum, is a key quantity to evaluate compound potency. For multi-donor dose-response data, it is often of interest to estimate the overall EC50 (i.e. the average EC50 of the population of donors) and its 95% confidence interval (CI). A few multi-donor EC50 estimation methods have been proposed in the literature. Jiang and Kopp-Schneider (2014) systematically compared the meta-analysis approach and the nonlinear mixed-effects approach and concluded that the meta-analysis approach is simple and robust to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments, while the nonlinear mixed-effects approach has the issue of convergence failures probably due to overparameterization. In this article, we propose a modification of the nonlinear mixed-effects approach by using the stochastic approximation expectation-maximization (SAEM) algorithm to estimate model parameters and using multiple starting points to search for globally optimal values, which can substantially alleviate the issue of convergence failures even for small number of donors (e.g. n = 3), and achieve a smaller absolute median bias and better coverage probability of 95% confidence interval than the meta-analysis approach when the number of donors is not too small (e.g. n ≥ 7).","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"1-16"},"PeriodicalIF":1.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Large-scale dependent multiple testing via higher-order hidden Markov models. 通过高阶隐马尔可夫模型进行大规模依赖多重测试

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-11-04 DOI: 10.1080/10543406.2024.2420657

Canhui Li, Jiangzhou Wang, Pengfei Wang

引用次数: 0

Different view of the diagnostics test accuracy measures and optimal cut-off point selection procedure under tree or umbrella ordering. 在树状排序或伞状排序下，诊断检测准确度测量和最佳截断点选择程序的不同视角。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-30 DOI: 10.1080/10543406.2024.2420659

Jing Kersey, Hani Samawi, Marwan Alsharman, Mario Keko, Haresh Rochani, Lili Yu, Jingjing Yin, Kelly Sullivan, Salaheddin Mustafa

{"title":"Different view of the diagnostics test accuracy measures and optimal cut-off point selection procedure under tree or umbrella ordering.","authors":"Jing Kersey, Hani Samawi, Marwan Alsharman, Mario Keko, Haresh Rochani, Lili Yu, Jingjing Yin, Kelly Sullivan, Salaheddin Mustafa","doi":"10.1080/10543406.2024.2420659","DOIUrl":"https://doi.org/10.1080/10543406.2024.2420659","url":null,"abstract":"In the realm of medical diagnostic testing, diagnostic tests can assume either binary forms, distinguishing between diseased and non-diseased states, or ordinal forms, categorizing states from non-diseased to various stages (1 to K). Another significant classification scheme for multi-class scenarios is tree or umbrella ordering, which entails several unordered sub-classes (subtypes) within a biomarker. Within tree or umbrella ordering, the classifier assesses whether the marker measurement for one class surpasses or falls below those for the other classes. Although Receiver Operating Characteristic (ROC) curves and summary measures have been adapted to accommodate tree and umbrella ordering, these approaches often yield cut-off points that generate highly sensitive tests for certain disease subtypes while compromising specificity for others. This may not be ideal for all diseases. Hence, in this investigation, we explore diverse measures of diagnostic test accuracy and optimal cut-off point selection procedures under tree or umbrella ordering to foster more specific tests. We present numerical examples and simulation studies and demonstrate the approach using real data on lung cancer.","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"1-31"},"PeriodicalIF":1.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small sample adjustment for inference without assuming orthogonality in a mixed model for repeated measures analysis. 在重复测量分析的混合模型中，无需假定正交性即可进行推理的小样本调整。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-29 DOI: 10.1080/10543406.2024.2420632

Kazushi Maruo, Ryota Ishii, Yusuke Yamaguchi, Tomohiro Ohigashi, Masahiko Gosho

{"title":"Small sample adjustment for inference without assuming orthogonality in a mixed model for repeated measures analysis.","authors":"Kazushi Maruo, Ryota Ishii, Yusuke Yamaguchi, Tomohiro Ohigashi, Masahiko Gosho","doi":"10.1080/10543406.2024.2420632","DOIUrl":"https://doi.org/10.1080/10543406.2024.2420632","url":null,"abstract":"The mixed model for repeated measures (MMRM) analysis is sometimes used as a primary statistical analysis for a longitudinal randomized clinical trial. When the MMRM analysis is implemented in ordinary statistical software, the standard error of the treatment effect is estimated by assuming orthogonality between the fixed effects and covariance parameters, based on the characteristics of the normal distribution. However, orthogonality does not hold unless the normality assumption of the error distribution holds, and/or the missing data are derived from the missing completely at random structure. Therefore, assuming orthogonality in the MMRM analysis is not preferable. However, without the assumption of orthogonality, the small-sample bias in the standard error of the treatment effect is significant. Nonetheless, there is no method to improve small-sample performance. Furthermore, there is no software that can easily implement inferences on treatment effects without assuming orthogonality. Hence, we propose two small-sample adjustment methods inflating standard errors that are reasonable in ideal situations and achieve empirical conservatism even in general situations. We also provide an R package to implement these inference processes. The simulation results show that one of the proposed small-sample adjustment methods performs particularly well in terms of underestimation bias of standard errors; consequently, the proposed method is recommended. When using the MMRM analysis, our proposed method is recommended if the sample size is not large and between-group heteroscedasticity is expected.","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"1-15"},"PeriodicalIF":1.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveraging real-world data to conduct externally controlled trial for rare diseases with count-type endpoints: utilizing multiple entries - a simulation study. 利用真实世界的数据开展以计数型终点为对象的罕见病外部对照试验：利用多个条目--一项模拟研究。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-27 DOI: 10.1080/10543406.2024.2420644

Tianyu Sun, Eileen Liao, Nan Shao, Junxiang Luo

{"title":"Leveraging real-world data to conduct externally controlled trial for rare diseases with count-type endpoints: utilizing multiple entries - a simulation study.","authors":"Tianyu Sun, Eileen Liao, Nan Shao, Junxiang Luo","doi":"10.1080/10543406.2024.2420644","DOIUrl":"https://doi.org/10.1080/10543406.2024.2420644","url":null,"abstract":"Conducting randomized controlled trials for medications targeting rare diseases presents significant challenges, due to the scarcity of participants and ethical considerations. Under such circumstances, leveraging real-world data (RWD) to generate supporting evidence may be accepted by the regulatory agency. Constructing an external control arm (ECA) from RWD for a single-arm trial has been conducted occasionally. A complication in this design is that patients from RWD may be eligible at multiple time points. Most studies approach this by selecting one time point as the index date for ECA patients. Here, we propose a novel design for externally controlled trials that permits the inclusion of ECA patients at various entry points. Accompanying this design, we make recommendations for statistical methods to account for measured confounders, limited sample size, within-subject correlation, and potential overdispersion inherent in count data. Furthermore, we present an idea for the blinding process for this type of study. We have conducted a series of simulations to assess the performance of the design and statistical methods in terms of bias, type I error, and efficiency, as compared to the approach of selecting only one entry per ECA patient. The study and parameter setup were based on a hypothetical case inspired by a rare disease study. The results indicate that allowing multiple entries for ECA patients can lead to enhanced performance in many aspects. It provides a controlled type I error, robustness against certain model misspecifications, and a moderate power improvement compared with selecting a single entry per ECA patient.","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"1-13"},"PeriodicalIF":1.2,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Issues in cox proportional hazards model with unequal randomization. 采用不等随机化的考克斯比例危险模型的问题。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-24 DOI: 10.1080/10543406.2024.2418139

Hongfei Li, Qian H Li, Chuan Tian, Kevin Hou

引用次数: 0

On approximate equality of Z-values of the statistical tests for win statistics (win ratio, win odds, and net benefit). 关于胜率统计（胜率、胜算和净收益）的 Z 值近似相等的统计检验。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-08 DOI: 10.1080/10543406.2024.2374857

Gaohong Dong, Ying Cui, Margaret Gamalo-Siebers, Ran Liao, Dacheng Liu, David C Hoaglin, Ying Lu

{"title":"On approximate equality of Z-values of the statistical tests for win statistics (win ratio, win odds, and net benefit).","authors":"Gaohong Dong, Ying Cui, Margaret Gamalo-Siebers, Ran Liao, Dacheng Liu, David C Hoaglin, Ying Lu","doi":"10.1080/10543406.2024.2374857","DOIUrl":"https://doi.org/10.1080/10543406.2024.2374857","url":null,"abstract":"Dong et al. (2023) showed that the win statistics (win ratio, win odds, and net benefit) can complement each another to demonstrate the strength of treatment effects in randomized trials with prioritized multiple outcomes. This result was built on the connections among the point and variance estimates of the three statistics, and the approximate equality of Z-values in their statistical tests. However, the impact of this approximation was not clear. This Discussion refines this approach and shows that the approximate equality of Z-values for the win statistics holds more generally. Thus, the three win statistics consistently yield closely similar p-values. In addition, our simulations show an example that the naive approach without adjustment for censoring bias may produce a completely opposite conclusion from the true results, whereas the IPCW (inverse-probability-of-censoring weighting) approach can effectively adjust the win statistics to the corresponding true values (i.e. IPCW-adjusted win statistics are unbiased estimators of treatment effect).","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"1-8"},"PeriodicalIF":1.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishment of RWS guidance reflecting contributions of China to regulatory science. 制定反映中国对监管科学所作贡献的 RWS 指南。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-01 Epub Date: 2024-03-17 DOI: 10.1080/10543406.2024.2330208

Jun Wang, Jie Chen, Jun Zhao, Ying Wu, Xiaona Xin, Pingyan Chen

引用次数: 0

Incorporating external real-world data (RWD) in confirmatory adaptive design. 将外部真实世界数据（RWD）纳入确认性适应设计。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-01 Epub Date: 2024-03-21 DOI: 10.1080/10543406.2024.2330212

Junjing Lin, Jianchang Lin

{"title":"Incorporating external real-world data (RWD) in confirmatory adaptive design.","authors":"Junjing Lin, Jianchang Lin","doi":"10.1080/10543406.2024.2330212","DOIUrl":"10.1080/10543406.2024.2330212","url":null,"abstract":"Adaptive designs, such as group sequential designs (and the ones with additional adaptive features) or adaptive platform trials, have been quintessential efficient design strategies in trials of unmet medical needs, especially for generating evidence from global regions. Such designs allow interim decision making and making adjustment to study design when necessary, meanwhile maintaining study integrity and operating characteristics. However, driven by the heightened competitive landscape and the desire to bring effective treatment to patients faster, innovation in the already functional designs is still germane to further propel drug development to a more efficient path. One way to achieve this is by leveraging external real-world data (RWD) in the adaptive designs to support interim or final decision making. In this paper, we propose a novel framework of incorporating external RWD in adaptive design to improve interim and/or final analysis decision making. Within this framework, researchers can prespecify the decision process and choose the timing and amount of borrowing while maintaining objectivity and controlling of type I error. Simulation studies in various scenarios are provided to describe power, type I error, and other performance metrics for interim/final decision making. A case study in non-small cell lung cancer is used for illustration on proposed design framework.","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"805-817"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The use of real-world data for clinical investigation of effectiveness in drug development. 利用真实世界的数据对药物开发的有效性进行临床调查。

IF 1.2 4区医学

Journal of Biopharmaceutical Statistics Pub Date : 2024-10-01 Epub Date: 2024-03-22 DOI: 10.1080/10543406.2024.2330215

Peijin Wang, Shein-Chung Chow

{"title":"The use of real-world data for clinical investigation of effectiveness in drug development.","authors":"Peijin Wang, Shein-Chung Chow","doi":"10.1080/10543406.2024.2330215","DOIUrl":"10.1080/10543406.2024.2330215","url":null,"abstract":"With the growing interest in leveraging real-world data (RWD) to support effectiveness evaluations for new indications, new target populations, and post-market performance, the United States Food and Drug Administration has published several guidance documents on RWD sources and real-world studies (RWS) to assist sponsors in generating credible real-world evidence (RWE). Meanwhile, the randomized controlled trial (RCT) remains the gold standard in drug evaluation. Along this line, we propose a hybrid two-stage adaptive design to evaluate effectiveness based on evidence from both RCT and RWS. At the first stage, a typical non-inferiority test is conducted using RCT data to test for not-ineffectiveness. Once not-ineffectiveness is established, the study proceeds to the second stage to conduct an RWS and test for effectiveness using integrated information from RCT and RWD. The composite likelihood approach is implemented as a down-weighing strategy to account for the impact of high variability in RWS population. An optimal sample size determination procedure for RCT and RWS is introduced, aiming to achieve the minimal expected sample size. Through extensive numerical study, the proposed design demonstrates the ability to control type I error inflation in most cases and consistently maintain statistical power above the desired level. In general, this RCT/RWS hybrid two-stage adaptive design is beneficial for effectiveness evaluations in drug development, especially for oncology and rare diseases.","PeriodicalId":54870,"journal":{"name":"Journal of Biopharmaceutical Statistics","volume":" ","pages":"818-841"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0